Amrinone

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Amrinone
Clinical data
Trade namesInocor
Other namesinamrinone (USAN US)
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailabilityn/a
Protein binding10 to 49%
MetabolismHepatic
Elimination half-life5 to 8 hours
ExcretionRenal (63%) and fecal (18%)
Identifiers
  • 5-amino-3,4'-bipyridin-6(1H)-one
JSmol)
  • O=C2C(/N)=C\C(\c1ccncc1)=C/N2
  • InChI=1S/C10H9N3O/c11-9-5-8(6-13-10(9)14)7-1-3-12-4-2-7/h1-6H,11H2,(H,13,14) checkY
  • Key:RNLQIBCLLYYYFJ-UHFFFAOYSA-N checkY
  (verify)

Amrinone, also known as inamrinone, and sold as Inocor, is a

inotropic effect of amrinone is mediated by the selective enhancement of high-gain CICR, which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A (PKA) and Ca2+ calmodulin kinase pathways.[3]

Actions

Increases cardiac contractility, vasodilator. Acts by inhibiting the breakdown of both cAMP and cGMP by the phosphodiesterase (

PDE3) enzyme. There is a long-standing controversy regarding whether the drug actually increases cardiac contractility in diseased myocardium (and therefore whether it is of any clinical use). The issue has been reviewed extensively by Dr Peter Wilmshurst, one of the first cardiologists and researchers to question the drug's efficacy.[4]

PDE-III inhibition and cardiac function

PDE III is present in cardiac muscle, vascular smooth muscle and platelets. PDE III degrades the phosphodiester bond in cAMP to break it down.

lusitropic effect. Both inotropic and lusitropic effects justify the use of amrinone to treat heart failure
. Amrinone decreases the pulmonary capillary wedge pressure while increasing cardiac output, as it functions as an arterial vasodilator and increases venous capacitance while decreasing venous return.[5] There is a net decrease in myocardial wall tension, and O2 consumption when using amrinone. Amrinone also has beneficial effects during diastole in the left ventricle, including relaxation, compliance and filling in patients with congestive heart failure.[5]

Indications

Short-term management of severe CHF (not used long term because of increased mortality, probably due to heart failure).

Effects in congestive heart failure

Congestive heart failure (CHF) is characterized by a reduction in ventricular performance and abnormalities in peripheral circulation and organs.

peripheral vascular resistance.[10]

Contraindications

Patients with aortic stenosis, hypertrophic cardiomyopathy, or history of hypersensitivity to the drug.

Precautions

May increase myocardial ischemia. Blood pressure, pulse, and ECG should be constantly monitored. Amrinone should only be diluted with normal saline or 1/2 normal saline; no dextrose solutions should be used. Furosemide, a loop diuretic, should not be administered into an IV line delivering amrinone.

Side effects

arrhythmias
and fever are other adverse effects.

Amrinone discovery and progression

Early studies in patients with heart failure showed that amrinone produced short-term hemodynamic improvement, but had limited long-term clinical benefit.[7] Some serious side effects of long term administration included sustained ventricular tachycardia resulting in circulatory collapse, worsening myocardial ischemia, acute myocardial infarction, and worsening congestive heart failure.[7][11] Amrinone has good absorption from the gastrointestinal tract [12] and has led to gastrointestinal upset when taken orally. The oral form of the drug is no longer in use.[11] Currently, only acute intravenous administration takes place.[11] The effects of amrinone vary widely with species and experimental condition; therefore, its inotropic effects are variable.[3] A loss in sensitivity to phosphodiesterase 3 inhibitors, including amrinone, has been observed in end stage heart failure in humans; other treatment options may be more useful for improvement in these stages.[3]

Naming

Amrinone is the INN, while inamrinone is the United States Adopted Name, which was adopted in 2000 in an attempt to avoid confusion with amiodarone.[13]

Synthesis

Amrinone synthesis:[14][15][16][17]

See also: Milrinone and Pelrinone.

References

  1. PMID 10478810
    .
  2. ^
    PMID 7246440
    .
  3. ^
    S2CID 6036283
    .
  4. ^ Wilmshurst P. "The HealthWatch Award 2003: Dr Peter Wilmshurst - "Obstacles to honesty in medical research"". Archived from the original on 2015-04-25.
  5. ^
    doi:10.1016/0888-6296(90)90226-6
    .
  6. ^
    PMID 2909994
    .
  7. ^
    S2CID 6325011
    .
  8. ^
    PMID 7379283
    .
  9. ^
    PMID 3004184
    .
  10. PMID 7350759
    .
  11. ^
    PMID 3530768
    .
  12. PMID 39684
    .
  13. ^ "Amrinone Becomes Inamrinone". USP Quality Review. 73. United States Pharmacopeia. March 2000. Archived from the original on 2008-10-03.
  14. ^ US Patent 4004012, Lesher GY, Opalka CJ, "3-Cyano-5-(pyridinyl)-2(1H)-pyridinones", issued 18 January 1977, assigned to STWB Inc. 
  15. ^ US Patent 4072746, Lesher GY, Opalka CJ, "3-Amino-5-(pyridinyl)-2(1H)-pyridinones", issued 7 February 1978, assigned to Aventis Pharmaceuticals Inc. 
  16. ^ US 4107315, Lesher GY, Opalka CJ, "5-(Pyridinyl)-2(1H)-pyridinones", issued 15 August 1978, assigned to Aventis Pharmaceuticals Inc. 
  17. ^ GB 2070008, Gelotte KO, Parady ED, "Process for preparing 5-cyano(3,4'-bipyridin)-6(1H)-one", published 3 September 1981, issued 18 April 1984, assigned to Sterling Drum Inc. 
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